Clade delineation and isolate-specific variability of Candida albicans exometabolome

Abstract

Abstract Candida albicans is a fungal pathobiont that relies on a vast molecular arsenal to navigate the host milieu and to confront the host immune defense. These molecular exchanges with the environment and the host are powered by a highly plastic metabolism, which is increasingly shown to vary between isolates. Unfortunately, metabolic variations are difficult to define in C. albicans as isolates (strains) are diverse and closely related. To overcome this constraint, we developed a high-throughput strategy to probe exometabolome variation in in vitro cultures of 95 clinical isolates from 12 major and five putative genetic clusters (clades). The workflow allows for the batch analysis of these isolates with robust replication (six or more replicates). Based on NMR (nuclear magnetic resonance) analysis of culture supernatants, we have shown delineation between clades, prominently clade 13 (corresponding to the so-called C. africana isolates) being metabolically distinct from the rest partly due to non-consumption of trehalose and weak utilization of choline. Further, using pairwise comparison, we could demonstrate that clades are delineated. We have also observed isolate-specific variation within clades, particularly in metabolites involved in central carbon metabolism. These results reveal C. albicans as a consortium of isolates with divergent metabolic phenotypes.